This invention is in the field of medicinal prevention and treatment of cancers and infections. In particular, it relates to a Chinese herbal formulation, ST 188L, and a method for the prevention and treatment of cancers and infections that comprises administering an effective dose of the herbal formulation. The raw materials for such formulation are Ecchinops grijissii, Cirsium segetum Bge, Solanum indicum Linn, Lonicerae flos, and Zizyphi fructus. 
Cancer is the second leading cause of death, next to cardiovascular disease, in the US. According to WHO, there are 31 million cancer sufferers worldwide, 10 million new cases, and 7 million die of it each year. The medical cost, care cost, and society cost are difficult to be estimated. Investigators continue to search for new therapeutic strategies for cancers.
The pathological and molecular mechanisms for cancer initiation and promotion have been revealed after decades of researches. There are many genes involved in the initiation and progression of cancers, some are oncogenic and some are tumor suppressive. Genetic, endocrinologic, immunologic, and environmental factors intertwine in the process of transformation and progression. Cancers are diseases caused by multi-factors under complex mechanisms.
The control and cure of cancers remain to be one of the most challenging health care tasks. Current modalities of therapies for cancers include surgery, radiotherapy, chemotherapy, gene therapy, immune therapy, or a combination of any of these treatments. Although surgery is the most effective way to eradicate tumor, when the patients are diagnosed with cancers, their tumors have substantially become inoperable. Current radiotherapy and chemotherapy modalities are unable to discriminate normal cells from neoplastic cells; therefore, there are apparent dose-limiting toxicities. Gene therapy is still at very early stage of clinical practice. Lately, immune therapy has shown very promising results.
Cancer cells are vulnerable to immune effector cells such as macrophages, natural killer cells (NK cells), and cytotoxic T lymphocytes (Vujanovic N L, Yasumura S, and Hirabayashi H., J. Immunol 1995; 154:281-9; Kuge S, Miura Y, Nakamura Y, Mitomi T, Habu S, and Nishimura T., J. Immunol 1995; 154:1777-85; and Nabioullin R, Sone S, Mizuno K:, J Leukocyte Biol 1994; 55:437-42. However, lymphocyte functions are suppressed in patients with cancer and in animal tumor models (Chouaib S, Asselin-Paturel C, Mami-Chouaib F, Caignard A., Immunol Today 1997; 18:493-7; and Wojtowiczpraga S., J. Immunother 1997; 20:165-77.). A reduction in immune competence due to suppressor cells including inhibitory T cells, macrophages, and immature bone marrow nonspecific suppressive cells has been correlated with reduced survival of patients and animals with cancer (Kaffenbeerger W, Holzer-Muller L, Auberger T, Clasen B P, Hohlmeier G, and van Beuningen D., Strahlenther Onkol 1995; 171:444-53; Aoe T, Okamoto Y, and Saito T., J. Exp. Med. 1995; 181:1881-6; and Young M R I, Schmidt-Pak A, Wright M A, Matthews J P, Collins S L, and Petruzzelli G., Clin Cancer Res.1995; 1:95-103). The induction and enhancement of immune activity most likely would have impact on cancer therapy. Most of the cancer patients eventually die of tumor metastasis. Many evidences demonstrate that NK cells and cytokines produced by NK cells inhibited tumor metastasis (Smyth M J, et al., J. Immunol. 1999; 162: 6658-6662; Takeda K, et al., J. Immunol. 1996; 156: 3366-3373; and Siders W M, et al., J. Immunol. 1998; 160: 5465-33735474).
NK cells respond to and are important in defense against a number of different infectious agents, including viruses, bacteria, protozoa, and parasites (Biron C A., Curr. Opin. Immunol. 1997; 9(1): 24-34; Unanue E R., Curr. Opin. Immunol. 1997. 9: 35-43; Scharton-Kersten T M, and Sher A., Curr. Opin. Immunol. 1997. 9: 44-51; Scharton-Kersten T M, and Sher A., Curr. Opin. Immunol. 1997. 9: 44-51; and Scott P, and Trinchieri G., Curr. Opin. Immunol. 1995. 7: 34-40). There are not many effective drugs for some of the infectious agents, for example, viruses. The emergences of drug resistant variants are one of the most difficult tasks for health care worldwide. NK cells participate in innate immunity and early defense within several hours to days after primary infections, whereas adaptive T and B cell responses develop after more than one week. Virus, such as arenaviruses (Welsh R M., J. Exp. Med. 1978. 148: 163-181), herpes viruses (Ching C, and Lopez C., 1979. Infect. Immun. 26: 49-56), orthomyxoviruses (Santoli D, Trinchieri G, and Koprowski H., 1978. J. Immunol. 121: 532-538), and picornaviruses (Godeny E K, and Gauntt C J., 1986. J. Immunol. 137: 1695-1702) induced interferon xcex1/xcex2 enhance NK cell-mediated cytotoxicity. NK cells can produce antimicrobial and immunoregulatory cytokines, such as interferon xcex3 (Orange J S, and Biron C A., 1996. J. Immunol. 156: 4746-47; and Orange J S, Wang B, Terhorst C, and Biron C A., 1995. J. Exp. Med. 182: 1045-1056). Low NK cell cytotoxic activity was linked with increased sensitivity to severe disseminating herpes infection (Biron C A, Byron K S, and Sullivan J L., 1989. N. Engl. J. Med. 320: 1731-1735; and Joncas J, Monczak Y, Ghibu F, Alfieri C, Bonin A, Ahronheim G, and Rivard G., 1989. J. Med. Virol. 28:110-117). There is also evidence showed that IL-2 increased LAK activity preferentially against HBV transfected HepG2-2215 cells when compared with parental HepG2 cells (Tsang T, Se C J, Yu M, and Tang, S L., 1994. Chung Hwa Yi Hsueh Tsa Chih 74(4):235-237).
The present invention involves the preparation and use of a formulation, ST 188L, a Chinese herbal medicine, on preventing and treating cancers and infectious diseases.
One aspect of the invention is to provide for a pharmaceutical composition for preventing and treating cancers comprising a formulation prepared ratably from a group of herbal plants consisting essentially of Ecchinops grijissii, Cirsium segetum Bge, Solanum indicum Linn, Lonicerae flos, and Zizyphi fructus in a pharmaceutically acceptable carrier or diluent. The Ecchinops grijissii, Cirsium segetum Bge, Solanum indicum Linn, Lonicerae flos, and Zizyphi fructus are prepared in this pharmaceutical composition respectively at a ratio of 5-15:2-6:2-6:1-10:1-5, preferably, at a ratio of 5:2:2:1:1. The formulation can be prepared in many desirable medicine dosage forms such as a tablet, soft gel, granule, powder, liquid, capsule or honey ball.
One more aspect of the invention is to provide for a method of providing therapeutical benefits to a recipient for preventing and treating cancers, which comprises the steps of preparing a pharmaceutical composition selected from extracts of a group of herbal plants consisting essentially of Ecchinops grijissii, Cirsium segetum Bge, Solanum indicum Linn, Lonicerae flos, and Zizyphi fructus; formulating said extracts in a pharmaceutically acceptable carrier or diluent in an amount sufficient to provide the intended therapeutical benefits; and administering said pharmaceutical composition to said recipient. The pharmaceutical composition is preferably administered by an oral route in a variety of desirable medicine dosage forms including, but without limitation to, a tablet, soft gel, granule, powder, liquid, capsule or honey ball. The amount of the pharmaceutical composition sufficient to provide the intended benefits is at the range of 0.75 g/Kg/day to 1.5 g/Kg/day.
One more aspect of the invention is to provide for a method and a pharmaceutical composition, that comprises the same ST 188L formulation prepared ratably from Ecchinops grijissii, Cirsium segetum Bge, Solanum indicum Linn, Lonicerae flos, and Zizyphi fructus in a pharmaceutically acceptable carrier or diluent at a ratio of 5-15:2-6:2-6:1-10:1-5, for enhancing endogenous immune system of a recipient. Evidence shows that the recipient""s endogenous immune system is enhanced due to the increase of natural killer cells and lymphokine activated killer cells.
One additional aspect of the invention is to provide for a pharmaceutical composition and a method of using it for preventing and treating infectious diseases. The pharmaceutical composition comprises a formulation prepared ratably from the group of herbal plants consisting essentially of Ecchinops grijissii, Cirsium segetum Bge, Solanum indicum Linn, Lonicerae flos, and Zizyphi fructus in a pharmaceutically acceptable carrier or diluent at a ratio of 5-15:2-6:2-6:1-10:1-5, and, preferably, at 5:2: 2:1:1. This pharmaceutical composition is suitable for preventing and treating infectious diseases caused by an infectious agent is a virus, bacteria, protozoa, or parasite.
Additionally, ST 188L was found to be non-toxic in vitro and was non-toxic in vivo up to 19.8 g/Kg in rats. ST 188L has been demonstrated efficacious in some cancer patients as evident in its ability of inducing NK cell activity and enhancing IL-2 induced lymphokine activated killer cell (LAK) activity in human peripheral blood mononuclear cells in vivo. As such, its anti-cancer activity mechanisms observed clinically were due to its immune modulation activity after metabolic activation in vivo. ST 188L incubated with K562 cells in vitro did not significantly modify K562 cells to become more susceptible to NK cells. In vitro treatment of PBMC with ST 188L somehow decreased its LAK activity. Thus, ST 188L appeared to be activated in vivo to stimulate the activity of NK cells and LAK cells. This was shown by the increases in cytolytic activity of PBMC isolated from volunteers after intake of ST 188L toward K562 and Daudi target cells in a dose dependent manner. Furthermore, intake of ST 188L also potentiated IL-2""s activity in a dose dependently. Consequently, the activation of NK and LAK activities by in vivo ST 188L administration can treat and prevent the occurrence, recurrence and metastasis of cancers, since NK and LAK cells are the first line of immune surveillance in vivo against cancers. The activation of NK and LAK activities by ST 188L in vivo may have activity in prevention and treatment of infectious agent, such as virus, bacteria, protozoa, and parasite infections.